title: Expression of p21WAF1 in Astler-Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy.
abstract: In several, but not all, previous studies, positive p21(WAF1) expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21(WAF1) expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler-Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21(WAF1) was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21(WAF1) was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21(WAF1) expression but not in the subgroup of 61 stage B2 patients with negative p21(WAF1) expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21(WAF1) expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21(WAF1) in colorectal tumor cells identifies a subgroup of Astler-Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy.
authors.affiliation: Department of Clinical Oncology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors.forename: Violetta
authors.initials: V
authors.lastname: Sulzyc-Bielicka
authors.forename: Pawel
authors.initials: P
authors.lastname: Domagala
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Urasinska
authors.forename: Dariusz
authors.initials: D
authors.lastname: Bielicki
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Wenancjusz
authors.initials: W
authors.lastname: Domagala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005472:Fluorouracil